Opioid Regulation of Pallidal Enkephalin Release: Bimodal Effects of Locally Administered Mu and DeltaOpioid Agonists in Freely Moving Rats
AbstractAbstract The globus pallidus and ventral pallidum receive dense enkephalinergic innervation from the dorsal and ventral striatum, respectively. A previous study demonstrated peripheral morphine administration to increase pallidal enkephalin release. To determine whether such opioid stimulatory effects may be mediated directly in the pallidum, in vivo microdialysis was used to study the effects of local administration of several concentrations of the mu receptor agonists morphine and morphine-6-glucuronide (M6G) as well as the the delta receptor agonist SNC80 on pallidal enkephalin release in freely moving rats. Low concentrations of morphine or M6G (1–10 nM) enhanced the release of enkephalins, an effect that was reversed by coadministration of the mu receptor antagonist β-funaltrexamine (β-FNA). A similar stimulatory effect was observed with a low concentration of SNC80 (50 nM), an effect that was blocked by the delta antagonist naltrindole (NTD). High concentrations of morphine (100 nM to 100 μM) had little or no effect, whereas M6G (10 μM) suppressed enkephalin release, an effect that was reversed by β-FNA. Similarly, a high concentration (5 μM) of SNC80 suppressed enkephalin release. However, this effect was not blocked by NTD but was attenuated by β-FNA, suggesting a mu receptor-mediated action. These results offer in vivo evidence of bimodal ( i . e ., stimulatory and inhibitory) effects of mu and delta opioid agonists on enkephalin release in the pallidum.